Effect of Crosslinking on the Properties and Stability of Andrographolide Solid Dispersions

Objectives: Crosslinking enhances solid dispersion (SD) stability but often restricts drug release, and this trade-off remains unresolved. In this study, crosslinked polyvinyl alcohol-suberic acid ester (CPSE) carriers with different crosslinking degrees were prepared to investigate the effects of crosslinking on the properties, dissolution and stability of andrographolide (AG)-SDs, aiming to identify crosslinking conditions that ensure both effective dissolution and improved stability. Methods: CPSE was prepared at 110 °C or 130 °C for 4, 8 or 12 h with uncrosslinked polyvinyl alcohol (PVA) as the control. AG-CPSE-SDs and AG-PVA-SD were compared in terms of AG relative crystallinity (RC), surface free energy, hygroscopicity, dissolution and stability. Stability was evaluated after 30-day storage at 40 ± 2 °C/75 ± 5% RH. Results: Compared with AG-PVA-SD, AG-CPSE-SDs showed higher RC but lower surface free energy and hygroscopicity. SDs with lower crosslinking degrees had dissolution profiles similar to AG-PVA-SD, whereas those with higher crosslinking degrees showed significantly reduced dissolution rates. After storage, the dense network in highly crosslinked SDs hindered water entry and diffusion and restricted AG migration and recrystallization, thereby conferring better hygroscopic stability, interaction stability, recrystallization stability and dissolution stability. Notably, the SD using CPSE crosslinked at 130 °C for 4 h as the carrier balanced effective dissolution and enhanced stability. Conclusions: By tuning the crosslinking degree, SD stability can be improved without sacrificing drug dissolution. Moderate rather than maximal crosslinking achieves the optimal balance, providing a practical strategy for designing crosslinked carriers for SDs.